The clinical use of antishock trousers.

In 34 (71%) of 48 consecutive patients who were in shock (systolic blood pressure less than 80 mm Hg) the application of antishock trousers by ambulance personnel or emergency room staff produced rapid increases of 20 mm Hg or more in the systolic blood pressure. The trousers were applied to a 49th patient only to stabilize a fractured femur. The most common indication for the device was shock resulting from hemorrhage in the upper gastrointestinal tract. Of 20 such patients, 17 (85%) responded rapidly, as did all 5 patients who were treated for a ruptured abdominal aortic aneurysm. The proper application and management of antishock trousers are simple enough for use in the field, although deflation of the device before adequate replacement of fluids would precipitate a return to a state of shock.     

Threshold of airway response to inhaled methacholine in healthy men and women

Threshold of airway response to inhaled methacholine was determined using maximum expiratory partial flow-volume curves in 21 men and 36 women with similar age distribution, all of them healthy nonsmokers. Mean threshold was on average 1.3 doubling dose lower in women than men. There were no sex differences in the increase of maximum expiratory flows after a full inspiration when the airways were constricted by methacholine.     

Haemodynamic response to exercise in healthy young and elderly subjects

Whereas with advancing age, peak heart rate (HR) and cardiac index (CI) are clearly reduced, peak stroke index (SI) may decrease, remain constant or even increase. The aim of this study was to describe the patterns of HR, SI, CI, arteriovenous difference in oxygen concentration (C _a-vO₂), mean arterial pressure (MAP), systemic vascular resistance index (SVRI), stroke work index (SWI) and mean systolic ejection rate index (MSERI) in two age groups (A: 20–30 years, n = 20; B: 50–60 years n = 20. After determination of pulmonary function, an incremental bicycle exercise test was performed, with standard gas-exchange measurements and SI assessment using electrical impedance cardiography. The following age-related changes were found: similar submaximal HR response to exercise in both groups and a higher peak HR in A than in B[185 (SD 9) vs 167 (SD 14) beats · min⁻¹, P < 0.0005]; increase in SI with exercise up to 60–90 W and subsequent stabilization in both groups. As SI decreased towards the end of exercise in B, a higher peak SI was found in A [57.5 (SD 14.0) vs 43.6 (SD 7.7) ml · m⁻², P < 0.0005]; similar submaximal CI response to exercise, higher peak CI in A [10.6 (SD 2.5) vs 7.2 (SD 1.3) l · min⁻¹ · m⁻², P < 0.0005]; no differences in C _a-vO₂ during exercise; higher MAP at all levels of exercise in B; higher SVRI at all levels of exercise in B; lower SWI in B after recovery; higher MSERI at all levels of exercise in A. The decrease in SI with advancing age would seem to be related to a decrease in myocardial contractility, which can no longer be compensated for by an increase in preload (as during submaximal exercise). Increases in systemic blood pressure may also compromise ventricular function but would seem to be of minor importance. Accepted: 24 September 1996     

Plasma adrenomedullin response to maximal exercise in healthy subjects.

The aim of the study was to find out whether maximal exercise performed by healthy young men influences plasma adrenomedullin concentration (ADM) and is the peptide level related to the cardiovascular, metabolic and hormonal changes induced by exercise. Ten subjects (age 24+/-1.0 yr) participated in the study. They performed graded bicycle ergometer exercise until exhaustion. Heart rate (HR) and blood pressure (BP) were measured throughout the test. Before and at the end of exercise venous blood samples were taken for [ADM], noradrenaline [NA], adrenaline [A], growth hormone [hGH], cortisol and lactate [LA] determination. Plasma [ADM] decreased during exercise from 1.71+/-0.09 to 1.53+/-0.10 pmol x l(-1) (p<0.01). This was accompanied by increases in plasma catecholamines and [hGH], while plasma cortisol level did not change. Positive correlation was found between the exercise-induced decreases in plasma ADM and diastolic BP. Blood [LA], systolic and mean BP at the end of exercise correlated negatively with plasma [ADM]. No significant interrelationships were found between plasma ADM, catecholamines or the other hormones measured. The present data suggests, that maximal exercise inhibits ADM secretion in young healthy men. Metabolic acidosis and a decrease in peripheral resistance might be involved in this effect.     

Circadian rhythm of the PRL response to TRH in healthy subjects

The PRL response to TRH constitutes an important clinical tool for diagnosing forms of hyperprolactinemic syndrome. Hence it is important to establish the characteristics of the circadian variation in the response of PRL to TRH to improve the diagnostic value of the test. Six male subjects, ranging in age from 23 to 24 years, participated in this study. All were considered healthy on the basis of clinical examination, biochemical and hormonal tests. Six TRH tests were performed on each subject, one test every other day during a total span of 12 days. Each test was performed at a different clock hour: 0000, 0400, 0800, 1200, 1600, 2000. For the test, subjects received 200 microgram TRH intravenously. Blood samples were drawn from a catheterized arm vein before the TRH injection (basal value) and 20, 30, 60 and 120 min after injection. At each timepoint 5 endpoints were determined for PRL on each subject. The population mean cosinor, according to Halberg, was used to investigate the circadian rhythm in each of the endpoints. All the 5 endpoints for PRL are consistent on showing p values near 0.5 and acrophase estimates before midnight (while basal value displays acrophase at 0400). Further investigations are necessary to clarify these circadian rhythms and the shift of the acrophases.     

Effects of pneumatic antishock garment inflation in normovolemic subjects

This study examines the effects of inflation of pneumatic antishock garments (PASG) in 10 normovolemic men (mean age 44 +/- 6 yr) undergoing diagnostic catheterization. Seven subjects had normal heart function and no evidence of coronary artery disease (CAD); three patients had CAD. High-fidelity multisensor catheters were employed to simultaneously record right and left heart pressures before PASG inflation and after inflation to 40, 70, and 100 mmHg. A thermal dilution catheter was used to obtain pulmonary capillary wedge pressure and cardiac output. Counterpressure increases greater than or equal to 40 mmHg were associated with significant changes in left and right heart pressures. Right and left ventricular end-diastolic pressures increased 100% (P less than 0.01); mean pulmonary arterial and aortic pressures increased 77 and 25%, respectively (P less than 0.01); systemic vascular resistance increased 22% (P less than 0.05) and pulmonary vascular resistance did not change in normal subjects at maximum PASG inflation. Heart rate, cardiac output, and aortic and pulmonary arterial pulse pressures did not change during inflation in either group. Right and left ventricular end-diastolic pressures and pulmonary capillary wedge pressure were greater (P less than 0.05) in the CAD group compared with the normal subjects during PASG inflation. The data suggest that the primary mechanism whereby PASG inflation induces changes in central hemodynamics in normovolemic subjects is through an acute increase in left ventricular afterload. PASG changes in afterload and pulmonary capillary wedge pressure imply that these devices should be used with caution in patients with compromised cardiac function.     

Adaptive immune response to lipoproteins of Staphylococcus aureus in healthy subjects

Staphylococcus aureus is a frequent commensal but also a dangerous pathogen, causing many forms of infection ranging from mild to life‐threatening conditions. Among its virulence factors are lipoproteins, which are anchored in the bacterial cell membrane. Lipoproteins perform various functions in colonization, immune evasion, and immunomodulation. These proteins are potent activators of innate immune receptors termed Toll‐like receptors 2 and 6. This study addressed the specific B‐cell and T‐cell responses directed to lipoproteins in human S. aureus carriers and non‐carriers. 2D immune proteomics and ELISA approaches revealed that titers of antibodies (IgG) binding to S. aureus lipoproteins were very low. Proliferation assays and cytokine profiling data showed only subtle responses of T cells; some lipoproteins did not elicit proliferation. Hence, the robust activation of the innate immune system by S. aureus lipoproteins does not translate into a strong adaptive immune response. Reasons for this may include inaccessibility of lipoproteins for B cells as well as ineffective processing and presentation of the antigens to T cells.     

Sprint interval running increases insulin sensitivity in young healthy subjects

High intensity cycling training increases oxidative capacity in skeletal muscles and improves insulin sensitivity. The present study compared the effect of eight weeks of sprint interval running (SIT) and continuous running at moderate intensity (CT) on insulin sensitivity and cholesterol profile in young healthy subjects (age 25.2 ± 0.7; VO(2max) 49.3 ± 1.2 ml·kg(-1)·min(-1)). SIT and CT increased maximal oxygen uptake by 5.3 ± 1.8 and 3.8 ± 1.6%, respectively (p < 0.05 for both). Oral glucose tolerance test (OGTT) was performed before and 60 h after the last training session. SIT, but not CT, reduced glucose area under curve and improved HOMA β-cell index (p < 0.05). Insulin area under curve did not decrease significantly in any group. SIT, but not CT, reduced LDL and total cholesterol. In conclusion, sprint interval running improves insulin sensitivity and cholesterol profile in healthy subjects, and sprint interval running may be more effective to improve insulin sensitivity than continuous running at moderate intensity.     

Tachyphylaxis to inhaled methacholine in normal but not asthmatic subjects

Methacholine inhalation tests measure airway responsiveness in asthmatic and normal subjects. Tachyphylaxis occurs with repeated methacholine inhalations in normal subjects. The purpose of this study was to examine the time course and mechanisms of methacholine tachyphylaxis in normal subjects and to determine whether this occurs in mildly asthmatic subjects. Fifteen normal and nine asthmatic subjects were studied on 2 study days, at least 48 h apart. Each day, two inhalation tests were carried out. On one day, subjects performed two methacholine inhalation tests 3 h later by a methacholine test. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1), (PC20). All normal subjects developed methacholine tachyphylaxis. The mean PC20 increased from 47.3 mg/ml (%SE 1.34) to 115.6 (%SE 1.51) (P less than 0.0001) in a 3-h interval. This increase lasted for greater than or equal to 6 h (P = 0.012). Asthmatic subjects did not develop methacholine tachyphylaxis. Their mean methacholine PC20s were 1.6 mg/ml (%SE 1.4) and 1.5 (%SE 1.4) (P = 0.75) 3 h later. In two other series of experiments, normal subjects were pretreated with the cyclooxygenase inhibitors indomethacin (100 mg/day) or flurbiprofen (150 mg/day) or a placebo for 3 days before two methacholine tests 3 h apart. Both indomethacin and flurbiprofen significantly inhibited the development of methacholine tachyphylaxis. These results confirm that methacholine tachyphylaxis occurs in normal subjects, lasts greater than or equal to 6 h, and may occur through the release of inhibitory prostaglandins. By contrast, methacholine tachyphylaxis does not occur in asthmatic subjects.     

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects.

Deep breaths taken before inhalation of methacholine attenuate the decrease in forced expiratory volume in 1 s and forced vital capacity in healthy but not in asthmatic subjects. We investigated whether this difference also exists by using measurements not preceded by full inflation, i.e., airway conductance, functional residual capacity, as well as flow and residual volume from partial forced expiration. We found that five deep breaths preceding a single dose of methacholine 1) transiently attenuated the decrements in forced expiratory volume in 1 s and forced vital capacity in healthy (n = 8) but not in mild asthmatic (n = 10) subjects and 2) increased the areas under the curve of changes in parameters not preceded by a full inflation over 40 min, during which further deep breaths were prohibited, without significant difference between healthy (n = 6) and mild asthmatic (n = 16) subjects. In conclusion, a series of deep breaths preceding methacholine inhalation significantly enhances bronchoconstrictor response similarly in mild asthmatic and healthy subjects but facilitates bronchodilatation on further full inflation in the latter.     

Asymptomatic Helicobacter pylori infection increases asymmetric dimethylarginine levels in healthy subjects

BACKGROUND: Chronic infections have been demonstrated to be early factors of atherosclerosis and cardiovascular diseases, and their relevance increases when they are caused by agents with extremely broad spectrum of disease outcome such as Helicobacter pylori. The consequent endothelial impairment leads to a reduced bioavailability of nitric oxide. Increasing evidences have pointed out that the endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine, defined as a risk factor for cardiovascular disease, may increase in infections and plays an important role impairing the vascular functions of the endothelium. Starting from these findings, we aim to investigate whether H. pylori may affect asymmetric dimethylarginine levels. MATERIALS AND METHODS: The study was carried out on a group of 186 subjects (age 46.2 +/- 14.9 years). We evaluated asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine, presence of H. pylori by 13C-urea breath test, and the main parameters of glyco and lipo metabolic balance. RESULTS: Increased levels of asymmetric dimethylarginine were found in H. pylori-positive subjects with respect to H. pylori-negative subjects (0.46 x/ / 1.13 versus 0.42 x/ / 1.23 mol/l, p < .001, respectively). No differences were detected in L-arginine levels between the two groups. Multiple regression analysis performed in H. pylori-positive subjects and H. pylori-negative subjects showed profound differences in the variables related to asymmetric dimethylarginine (R2 = 66.9%, p < .01 versus 34.3%, p < .01, respectively) and symmetric dimethylarginine (R2 = 39.2%, p < .01 versus 20.6%, p = .09, respectively) levels. CONCLUSIONS: Our data clearly demonstrate that H. pylori infection increases asymmetric dimethylarginine levels. Moreover, this infection causes a profound metabolic modification that alters the role of the known determinants of asymmetric dimethylarginine levels. We conclude that H. pylori infection must be taken into account as a cause of increased asymmetric dimethylarginine levels and that the eradication of H. pylori may therefore lead to a decrease in asymmetric dimethylarginine levels, which is a further reason for the reduction of the risk for cardiovascular disease in this large portion of population.     

Cognitive training increases platelet PLA2 activity in healthy elderly subjects

Phospholipases A(2) (PLA(2)) are ubiquitous enzymes involved in membrane fatty acid metabolism and intracellular signalling. Recent studies have shown that PLA(2) subtypes are implicated in the modulation of pathways related to memory acquisition and retrieval. We investigated the effects of cognitive training on platelet PLA(2) activity in healthy elderly individuals. Twenty-three cognitively unimpaired older adults were randomly assigned to receive memory training or standard outpatient care only. Both groups were cognitively assessed by the same protocol, and the experimental group (EG) underwent a four-session memory training intervention. Pre- and post-test measures included prose and list recall, WAIS-III digit symbol, strategy use measures and platelet PLA(2) group activity. After cognitive training, patients in the EG group had significant increase in cytosolic, calcium-dependent PLA(2) (cPLA(2)), extracellular (or secreted), calcium-dependent PLA(2) (sPLA(2)), total platelet PLA(2) activity, and significant decrease in platelet calcium-independent PLA(2) (iPLA(2)) activity. Our results suggest that memory training may have a modulating effect in PLA(2)-mediated biological systems associated with cognitive functions and neurodegenerative diseases.     

Antigen challenge of sensitized rats increases airway responsiveness to methacholine

We measured airway responsiveness to methacholine (MCh) of highly inbred rats before and after six inhalational challenges with antigen. Ten Brown-Norway rats (130-216 g) that were actively sensitized to ovalbumin (OA) received six challenges with OA at 5-day intervals beginning 19 days after sensitization. An aerosol of OA (5% wt/vol) was inhaled for 1, 2, 5, and 10 min or until pulmonary resistance (RL) increased by at least 50%. Challenges with aerosolized MCh were performed immediately before and 14 days after sensitization, 2 days after the 3rd OA exposure, and 2, 7, 12, and 17 days after the 6th OA challenge. Four unsensitized rats underwent inhalational challenges with MCh over an equivalent time period. Responsiveness to MCh was calculated as the concentration of MCh required to increase RL to 200% of the control value (EC200RL). Seven out of 10 rats in the experimental group reacted to the first OA challenge with an immediate increase in RL of greater than 50% of control (range 70-550%). Three animals were unreactive to OA. Base-line EC200RL for all rats undergoing sensitization was 2.13 mg/ml (geometric mean), and it did not change significantly after sensitization (2.05 mg/ml). However, EC200RL of the rats that reacted to OA (n = 7) decreased significantly after 3 (1.11 mg/ml; P less than 0.005) and 6 OA exposures (0.96 mg/ml; P less than 0.005). The increase in responsiveness to inhaled MCh was present 17 days after the last OA exposure (EC200RL = 1.40 mg/ml; P less than 0.05). EC200RL of neither the unreactive sensitized rats (n = 3) nor the control rats (n = 4) changed after OA challenges.(ABSTRACT TRUNCATED AT 250 WORDS)     

Body position and the neuroendocrine response to insulin-induced hypoglycemia in healthy subjects

Changes in body fluid distribution are known to influence neuroendocrine function. The aim of the present study was to test the hypothesis that changes in plasma volume affect the counterregulatory neuroendocrine response to hypoglycemia. The tests were performed in 12 subjects in two situations: 'head-up' (+60 degrees head-up tilt standing for 30 min and hypoglycemia in sitting position afterwards) and 'leg-up' (leg-up position for 30 min and hypoglycemia in leg-up position afterwards) in a random order. Insulin-induced hypoglycemia was adjusted to 2.7 mmol/l for 15 min by glucose infusion. Plasma volume was greater by 2.2% (p < 0.001) in leg-up and lower by 9.6% (p < 0.001) in head-up position compared to the basal value in sitting position. Head-up position was associated with increases in ACTH, aldosterone, norepinephrine levels and plasma renin activity (p < 0.01). Leg-up position resulted in decreases in plasma growth hormone and epinephrine concentrations (p < 0.05). Except epinephrine, the neuroendocrine response to hypoglycemia, if any, was mild. Hypoglycemia failed to activate ACTH release after head-up position. Body fluid redistribution did not modify hormonal changes during insulin hypoglycemia. In conclusion, we suggest that body position and accompanying plasma volume changes do not appear to affect neuroendocrine and counterregulatory responses to moderate, short duration hypoglycemia in healthy subjects.